Peripheral nerve depends on nerve blood flow (NBF) for its energy requirements. Since mammalian peripheral nerve does not autoregulate, NBF is critically dependent on intercapillary distance, structure, sympathetic innervation, and on extraneural factors such as BP, and viscosity. In the edematous neuropathies such as Dejerine Sottas neuropathy, hypertrophic Charcot-Marie-Tooth disease and prednisone-responsive-hereditary-motor-and-sensory-neuropathy there is the potential of endoneurial hypoxia secondary to increased intercapillary distance. Alterations in sympathetic innervation, capillary structure and blood viscosity also occur in human peripheral neuropathies. It is therefore important to examine the physiology of NBF in normal and abnormal nerves. The broad hypothesis to be tested is that ischemic neuropathy develops when nerve blood flow is reduced in magnitude and duration beyond its ischemia safety factor. We postulate that nerve ischemia safety factor may be definable in terms of the stress, the nerve blood flow response and the metabolic effects if these were quantitated. We therefore propose to do the following studies on nerve blood flow. 1) The effect of sympathetic stimulation and section on nerve blood flow. 2) The effect of nerve stimulation on nerve blood flow. 3) The effects of blood pressure reduction on nerve blood flow and energy metabolism. 4) The effect of microemboli on nerve blood flow and energy metabolism. 5) To determine if there is a differential effect of ischemia on the center and the periphery of the fascicle under perturbations listed in 3 and 4. We will examine if there is a radial topographic distribution in NBF in edematous nerves. To do the last two studies, NBF will be recorded simultaneously using micropipets inserted into the center of the fascicle and into the subperineurial region of the fascicle. 6) Pari passu with the above recordings measurements of nerve lactate (an index of anerobic metabolism) and nucleotide phosphates (adenosine triphosphate and creatine phosphate) will be made to provide an estimate of the effects of ischemia on energy metabolism.